Contradictory to its effects on thrombin,C1-inhibitor reduces plasmin generation in the presence of thrombomodulin

Journal of Thrombosis and Thrombolysis - C1-inhibitor (C1INH) was shown to enhance thrombin generation (TG) in the presence of thrombomodulin (TM) by reducing production of activated protein C....     

The effect of patient ethnicity on the accuracy of peripheral pulse oximetry in patients with COVID-19 pneumonitis: a single-centre,retrospective analysis

Pulse oximetry is used widely to titrate oxygen therapy and for triage in patients who are critically ill. However, there are concerns regarding the accuracy of pulse oximetry in patients with COVID-19 pneumonitis and in patients who have a greater degree of skin pigmentation. We aimed to determine the impact of patient ethnicity on the accuracy of peripheral pulse oximetry in patients who were critically ill with COVID-19 pneumonitis by conducting a retrospective observational study comparing paired measurements of arterial oxygen saturation measured by co-oximetry on arterial blood gas analysis (SaO₂) and the corresponding peripheral oxygenation saturation measured by pulse oximetry (S_pO₂). Bias was calculated as the mean difference between SaO₂ and S_pO₂ measurements and limits of agreement were calculated as bias ±1.96 SD. Data from 194 patients (135 White ethnic origin, 34 Asian ethnic origin, 19 Black ethnic origin and 6 other ethnic origin) were analysed consisting of 6216 paired SaO₂ and S_pO₂ measurements. Bias (limits of agreement) between SaO₂ and S_pO₂ measurements was 0.05% (−2.21–2.30). Patient ethnicity did not alter this to a clinically significant degree: 0.28% (1.79–2.35), −0.33% (−2.47–2.35) and −0.75% (−3.47–1.97) for patients of White, Asian and Black ethnic origin, respectively. In patients with COVID-19 pneumonitis, S_pO₂ measurements showed a level of agreement with SaO₂ values that was in line with previous work, and this was not affected by patient ethnicity.     

Associations between anthropometric indicators in early life and low-grade inflammation,insulin resistance and lipid profile in adolescence

Background and aimsThe long-term relations between excessive adiposity in early childhood and unfavourable cardiometabolic profiles in later ages are not yet completely understood. We aimed to assess the associations between birth weight (BW) and BMI from 6 months to 6 years of age, with biomarkers indicative of low-grade inflammation, insulin resistance and lipid profiles in adolescence.Methods and resultsRetrospective school-based study with 415 Portuguese adolescents (220 girls), mean age of 14.08 ± 1.6 years old. Anthropometric data from birth to 6 years old was extracted from individual child health book records. Actual weight and height were measured and BMI calculated. Participants were classified at each time point as normal weight or overweight according to WHO reference values. Biomarkers were obtained from venous blood samples. Linear regressions were used to explore the associations between the biomarkers and early life anthropometric indicators. From 2 years onwards, BMI associated positively with the inflammatory score and HOMA-IR in adolescence. Children who were overweight/obese from 2 to 6 years of age presented significantly higher inflammatory score and HOMA-IR later in adolescence. TC/HDL ratio was also positively associated with BMI from the age of 5 years onwards. The associations between BMI and cardiometabolic outcomes remained positive in adolescence, with overweight adolescents presenting a higher inflammatory score, HOMA-IR and TC/HDL than normal weight adolescents.ConclusionA high BMI from an early age was consistently associated with worse inflammatory and lipid profiles and insulin resistance in adolescence. No associations were found between BW and the same studied outcomes.     

Neutrophil proteases degrade autoepitopes of NET-associated proteins

Neutrophils can form neutrophil extracellular traps (NETs) to capture microbes and facilitate their clearance. NETs consist of decondensed chromatin decorated with anti-microbial proteins. Here, we describe the effect of neutrophil proteases on the protein content of NETs. We show that the neutrophil serine proteases degrade several neutrophil proteins associated with NETs. Interestingly, the anti-bacterial proteins associated with NETs, such as myeloperoxidase, calgranulin B and neutrophil elastase (NE), seem to be less susceptible to proteolytic degradation than other NET proteins, such as actin and MNDA. NETs have been proposed to play a role in autoimmune reactions. Our data demonstrate that a large number of the autoepitopes of NET proteins that are recognized by autoantibodies produced by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients are also removed by the proteases. In conclusion, neutrophil serine proteases have a major impact on the NET proteome and the proteolytic changes of NET-associated proteins may counteract autoimmune reactions to NET components.     

Epithelial ovarian cancer risk: A review of the current genetic landscape

Ovarian cancer is the fourth most common cause of cancer-related death in women in the developed world, and one of the most heritable cancers. One of the most significant risk factors for epithelial ovarian cancer (EOC) is a family history of breast and/or ovarian cancer. Combined risk factors can be used in models to stratify risk of EOC, and aid in decisions regarding risk-reduction strategies. Germline pathogenic variants in EOC susceptibility genes including those involved in homologous recombination and mismatch repair pathways are present in approximately 22% to 25% of EOC. These genes are associated with an estimated lifetime risk of EOC of 13% to 60% for BRCA1 variants and 10% to 25% for BRCA2 variants, with lower risks associated with remaining genes. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) thought to explain an additional 6.4% of the familial risk of ovarian cancer, with 34 susceptibility loci identified to date. However, an unknown proportion of the genetic component of EOC risk remains unexplained. This review comprises an overview of individual genes and SNPs suspected to contribute to risk of EOC, and discusses use of a polygenic risk score to predict individual cancer risk more accurately.     

Eficacia de la terapia con señales electromagnéticas pulsadas y transmitidas de manera dieléctrica monopolar en procesos dolorosos asociados a esclerosis múltiple. Estudio piloto

IntroductionPain is highly prevalent in patients with multiple sclerosis (MS); it is chronic in 50% of cases and is classified as nociceptive, neuropathic, or mixed-type. Pain affects quality of life, sleep, and the activities of daily living. Electrotherapy is an interesting alternative or complementary treatment in the management of pain in MS, with new innovations constantly appearing.Material and methodsThis study evaluates the effectiveness of treatment with monopolar dielectric transmission of pulsed electromagnetic fields (PEMF) for pain associated with MS. We performed a randomised, placebo-controlled clinical trial including 24 patients, who were assessed with the Brief Pain Inventory, the Multiple Sclerosis International Quality of Life questionnaire, the Beck Depression Inventory, and the Modified Fatigue Impact Scale.ResultsStatistically significant improvements were observed in maximum and mean pain scores, as well as in the impact of pain on work, personal relationships, and sleep and rest. Not significant differences were found between the treatment and placebo groups.ConclusionsTreatment with PEMF may be effective in reducing pain in patients with MS, although further research is necessary to confirm its effectiveness over placebo and to differentiate which type of pain may be more susceptible to this treatment.